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For the mission in the Soell system, the ship's more likable, fully functional, three-year old onboard AI Chauncey was replaced by a six-year old artificial intelligence called Rebecca.[3] Unbeknownst to the crew, Rebecca's mission was to ensure that the Flood did not escape containment in the case the prisoner transportMona Lisa, which had been used by ONI to conduct experiments on the Flood, had been compromised.

While stationed at the derelict Installation 04, the Red Horse's crew picked up several cryo chambers from the UNSC Pillar of Autumn, finding most of the occupants dead.[3] After searching the debris field for three days, they came across a single escape pod that had been launched from the Mona Lisa, which was drifting in the debris field. Inside the pod was one man who had manged to escape from the prison ship; however, he died soon after being rescued.[4]

Foucault was ordered by Rebecca to send a squad of 18 Marines led by SergeantZhao Heng Lopez to the Mona Lisa to investigate. However, a Covenant ship soon arrived, making any backup impossible.[5] Once the Marines were aboard the ship, it was quickly discovered that the Mona Lisa had been overcome by the Flood. The mission saw the deaths of all but one marine, as well as an ONI operative responsible for the outbreak; the Red Horse retrieved both survivors soon after. Eventually, the Red Horse was forced to destroy the prison ship with a Shiva-class nuclear missile in order to contain the Flood.[6]

In the motion comic adaptation of The Mona Lisa, the Red Horse is depicted as lacking any form of visual active camouflage, and has numerous lights shining across its hull, making it conspicuously visible to the naked eye. While it may be inferred that the ship was cloaked from sensors outside the visible spectrum, prowlers have also been established to use photo-reactive coating as a form of active camouflage. Thus, it would be unlikely that such systems would not be in use during the Red Horse's sensitive mission in Alpha Halo's debris field, particularly after the appearance of a Covenant ship in the system. The lack of active camouflage may be a liberty taken for the sake of presentation.

Like the UNSC Dusk, the RedHorse was manned by regular Navy personnel instead of ONI personnel.